Cells invade the vitreous from the retina with disease or injury, and from other extravitreal tissues, such as the sclera, with perforating ocular trauma. The invasive cells can form dense vitreal membranes that contribute to tracrion detachment of the retina and blindness. Vitreal hemorrhage promotes complex vitreal lesions, but the mechanism of this blood-mediated aggravation is unknown. The hypothesis of this proposal is that the release of mitogenic agents, as a direct of indirect result of hemorrhage promotes proliferation in invasive cells. Cell multiplication increases strand size and, therefore, vitreal pathology. Mitogenic agents of potential interest include factors released from blood platelets and those activated by phagocytic cells. Platelet release is likely to occur within the vitreous after hemorrhage and phagocytes invade the hemorrhagic vitreous to remove debris. Both platelet and macrophage--derived mitogens may have biological roles in other diseases or injuries, but no role in posterior ocular pathology has been demonstrated. The aim of the proposed research is to determine if calls from the rabbit neural retina, retinal pigment epithelium or sclera respond to either of these mitogens. Responses will be assessed by microscopy both in vitro and in cells introduced into the vitreous. Invasive cells in vitreal membranes are sometime associated with a newly synthesized collagen matrix that differs morphologically from normal vitreous matrix. Since collagen deposition may be significant for dense strand formation, factors which promote collagen synthesis would also contribute to lesion severity. Evidence indicates that platelet and macrophage--derived mitogens might increase collagen synthesis either directly, or as a result of stimulating the number or general protein synthetic activity of target cells. The proposed research also aims to investigate by biochemical procedures the effect of these factors on the type and amount of collagen synthesized by invasive cells in vitro and in vivo. Determination of the effects of vitreal hemorrhage on cell proliferation and protein secretion will aid the long range goal of impeding the responses to vitreal bleeding that promote or accelerate vision loss.